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There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study he is presenting at CROI 2008.

My name is Lawrence Siegel. I'm an infectious disease fellow at the Center for Special Studies in Chelsea, New York and we're affiliated with Weill Cornell Medical College. I'm going to be talking about my poster today on the clinical presentation of syphilis in HIV-infected men who have sex with men in an urban clinic.1

Lawrence Siegel, M.D., M.P.H.

The background information about this study is essentially that, since 2000, there have been increasing cases of early syphilis in urban centers throughout the world. Particularly in New York City, we're having a tremendous increase in cases. Despite a lot of prevention work and outreach by the New York Department of Health, 2007 saw a doubling of the number of early syphilis cases.

Our clinic in Chelsea is actually the location of the [country's] highest incident rate of syphilis, so while the nation is experiencing somewhere [between] about two to three per 100,000 cases, Chelsea in New York City has about 70 per 100,000.

In our clinic we were seeing a lot of patients who, instead of coming to the doctor with symptomatic complaints of syphilis, were just having incidental positive tests. We set out to see if these patients somehow presented earlier with their syphilis symptoms and we just missed it.

In addition, we were going to look at RPR [(rapid plasma regain) titer] responses after treatment to see if people are responding to treatment and if there was any difference among the treatments.

The only patients included in this study were [HIV-infected] patients who never had syphilis before, so they could not have told their physician they had syphilis, and they could not have positive RPR upon initiation or positive FTA [fluorescent treponema absorption].

One hundred eighteen men were included in the study, with a median age of about 38. Participants were fairly racially diverse, reflective of our clinic -- about 33% Caucasian, 30% African American, and 34% Latino. Most of them were early diagnoses, so only 11% were late latent and the other most popular categories were about 70% with secondary syphilis. Most of them had titers in the 32% to 64% range.

It turns out that although there were 11% [with] latent [infection], only about 8% of the patients were asymptomatic. The most common symptom that was noticed was generalized rash. About 60% of the patients presented with that and about 23% of them had a delay in their diagnosis. About 23% of those 70 people presented at some earlier time and there was a median delay [in diagnosis] of 25 days. While that was the most common symptom, the more interesting finding in the study is that patients are presenting earlier and with more atypical symptoms. Things like sore throat and cervical lymphadenopathy were noticed in 21% and 19% of patients respectively.

About half of the patients in those groups had diagnostic delays, and the delay was about 44 or 56 days prior to their diagnosis. There were a few months in between where they had infectious syphilis that wasn't diagnosed or was misdiagnosed. Other symptoms that people had were subjective fever, inguinal lymphadenopathy, mouth ulcers, and then also missed chancres.

Other analyses that we did were just to look at the resolution of the RPR by stage of diagnosis, so whether you had early syphilis, any stage, you were no more likely to have a delayed resolution of your RPR. The people who did have delayed were the late latents.

In terms of treatment, for any early syphilis, meaning primary, secondary, early, latent, it did not matter whether you got one shot of penicillin, three shots, or took doxycycline. Your RPR became negative at the same rate.

As far as the four-fold decrease [in RPR titers], about 96% of patients had a four-fold decrease overall, so a very good response. The re-infection rates were also quite high -- about 24% of this cohort became re-infected.

How quickly?

It's about 10% a year, re-infection, and then in a follow-up study we'll talk about, about 10% of this group goes on to have a second and sometimes third infection.

In conclusion, basically, the syphilis epidemic is going on in Chelsea and is getting worse in the context of outreach. The presentation of syphilis is characterized by a wide range of symptoms that physicians are not necessarily picking up at the time of presentation, including atypical things like sore throat and cervical lymphadenopathy. It does look like primary, secondary or early latent syphilis does respond by RPR. Patients with late latent respond slower and reinfection is quite common. So we are recommending that providers do more regular screening, at least every three months, to increase awareness of possible presenting symptoms.

This is in all HIV-infected patients or just MSM?

At New York Hospital, the only syphilis cases we had were in HIV-infected men who have sex with men. We had no other cases.

What is your feeling about this? What do you think is going on to cause this increased rate? Do you think it could be methamphetamine that is causing this behavior? There have been a couple of studies here about small groups of men that are passing hepatitis C. So is that kind of similar to this?

There are definitely a couple things going on. There definitely seems to be a very high-risk group of men who have sex with men who are getting infected repeatedly and then other groups who just get infected once or not at all. I guess the real intriguing question is why this really took off in the year 2000 as opposed to any other time. I think there are probably a couple things going for that. The first is probably condom fatigue and the fact that probably unsafe sex -- which has been well documented all over this conference -- is back on the rise.

But the other thing that happened in the year 2000, which has been discussed here, is the use of the Internet for sex, which has increased the efficiency and the number of partners. That really is the year [when rates of unsafe sex started to rise] -- the Internet became much more popular. The other thing here is that, because we see these sore throat cervical symptoms, there's probably a lot more oral sex. Getting people to use condoms for oral sex has never been successful. So those few things together.

Are men aware that they can get syphilis in the back of their throat?

For the most part, people are surprised when they hear it. Our nurses see all the patients for prevention visits for their penicillin shots and they do the education around that. But most men are surprised that they can get syphilis through oral sex.

How does this compare to the incidence of other sexually transmitted diseases, like gonorrhea? I know this wasn't part of the study, but in the clinic, is that just as common?

It's not nearly as common. Coinfection was pretty rare, maybe there were a handful of people, but we definitely have plenty of gonorrhea cases. I don't know those exact numbers.

Why would syphilis be much more common in this population if the activity could get any number of things like herpes, or any other infections?

It's a good question. It could be the fact that [syphilis] is very infectious. I don't know if gonorrhea is more or less infectious than syphilis, but when you have a positive RPR and you're in that secondary phase, it's very contagious because it's in the bloodstream and so any of these mucus membrane exposures [could transmit syphilis].

Do you know of any awareness projects in New York now about this?

There were awareness projects going on in New York City to providers. I don't know if there's anything new because they just released these new data that there was a doubling of the rate in the first quarter of 2007. There was significant outreach done.

Was this outreach only to providers? Or to patients as well?

There were community outreaches also. It's available on the New York City Department of Health website and what was done in the neighborhood.

It's very disheartening to see. This is all an HIV-infected population. It means that not only are they getting syphilis but they might be transmitting HIV.

Yes. It's about 60% of these men are HIV coinfected in New York City. So there are 40% who are also just MSM. But yes, it is discouraging unsafe behavior which probably also indicates why HIV transmission is continuing in certain areas of New York City also.

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